DESCRIPTION: A variety of factors, including microbial, genetic, immunological, behavioral and environmental, may interact to contribute to dental caries development. One feature that has hampered better understanding of caries etiology and natural history is the inability within most studies to date, to account for a variety of potential effect modifiers. These include poor characterization of the study participants' exposure to fluoridated water, other sources of topical fluoride, utilization of professional dental care, and other factors that may alter disease development and progression. In response to these deficiencies, the National Institutes of Health has recently commissioned a Consensus Development Conference on the Diagnosis and Management of Dental Caries throughout. Some of the key recommendations from this conference to be addressed by this application include: 1) early identification of populations at risk for developing dental caries such as young children; 2) longitudinal studies on the natural progression of dental caries; 3) research on emerging techniques for the diagnosis of dental caries; and 4) genetic studies and characterization of genetic markers for dental caries. To date, our investigative team has assembled a cohort of 322 twin pairs (644 individuals) 18 months to 7 years of age and of low socioeconomic status residing in the city of Montes Claros, State of Minas Gerais, Brazil. A large proportion of these children are caries active and without access to professional dental care and thus far their caries has remained untreated. In addition, they have no access to fluoridated water or professionally administered topical fluorides. The primary goal of this proposal is to determine, in cross-sectional and prospective data, the relative contribution of genetic and environmental factors to individual variation in liability to early dental caries, including its phenotypic stability and change. To enable this research, we will thoroughly characterize structural changes in enamel from pre-cavitated lesions to surface collapse. In this investigation we propose to study dental caries traits in young twins with the following specific aims: Specific Aim 1- to recruit and examine 500 twin pairs, in the age range of 18 months to 7 years; Specific Aim 2- to characterize dental caries phenotypic expression by detailing its onset and progression; Specific Aim 3- to determine the relative role of heredity and environment in phenotypic variation related to the onset and progression of dental caries. To our knowledge, this study will be the first to examine the genetic and environmental composition of variation in caries development, employing a comprehensive set of clinical measurements. The results obtained in this study, by identifying the most heritable traits, will inform research that will employ molecular genetic analyses for dental caries surface-specific traits in the same twin sample.